DESCRIPTION: The investigators have identified a subregion of chromosome 3q that undergoes tumor-specific loss of constitutional heterozygosity (LoH) at high frequency during osteosarcoma tumorigenesis. LoH is frequently associated with the presence of tumor suppressor gene within the region of LoH. A bone dysmorphology syndrome Brachmann-DeLange syndrome also maps to this region suggesting that the tumor suppressor gene and the locus for the dysmorphology syndrome may be the same gene. Thus the specific aims of this proposal are: 1) To isolate candidate cDNAs from within the D3S1212-D3S1246 region; 2) To character the candidate cDNAs for expression patterns consistent with osteosarcoma tumor suppressor gene activity; 3) To conduct mutational analysis in osteosarcoma tumors on those candidate cDNAs with expression patterns consistent with osteosarcoma tumor suppressor gene activity; 4) to conduct mutational analysis for inherited mutations in familial osteosarcoma and Brachmann-DeLange syndrome patients.